Lowering Bladder Cancer Recurrences: What the Evidence Shows

Bladder cancer, the most common malignancy of the urinary tract, can be quite difficult to detect or diagnose.  The vast majority of patients are diagnosed with a non-muscle-invasive form of bladder cancer, and this has a fairly high recurrence rate—approximately an 80% probability of relapse within five years.  It is due to this inordinately high recurrence rate that bladder cancer is considered to be the most expensive cancer to treat.

In the past few decades, the standard tool for diagnosis has been cystoscopy.  This procedure entails passing an endoscope through the urethra in order to examine the interior of the bladder.  The scope can then be used to guide the surgery itself using what’s called transurethral resection.

There’s a problem with the standard cystoscopy approach: It can miss or overlook many bladder tumors.  By recent estimates, one out of every three tumors may be missed due to the inconspicuous flat form and small size of those tumors.

A promising solution is photodynamic diagnosis (PDD or photodiagnosis), which improves the detection rates for inconspicuous bladder cancer.  This involves the use of a photosensitizer that is instilled into the bladder and selectively accumulates in abnormal or malignant tissue.  The malignant tissue emits a red color upon exposure to blue light.  Normal tissue appears blue.

This particular PDD method is referred to as either fluorescence cystoscopy or PDD/blue light cystoscopy.  But just how effective is the PDD approach?   To answer this question, researchers at West China Hospital and Sichuan University in Sichuan (China) recently conducted a meta-analysis of all the evidence obtained from randomized controlled trials, the gold standard of medical “proof”.

Drawing from various databases, the Sichuan researchers identified a dozen randomized controlled trials that enrolled a total of 2258 patients.  Their analysis found that patients who underwent PDD/blue light cystoscopy had a 50% lower rate of recurrences compared to patients receiving white light cystoscopy.  In other words, recurrences were cut in half thanks to the PDD approach.

Moreover, the time to the first recurrence was significantly delayed (by nearly 7.5 weeks) in the PDD group, and the lower recurrence rate was statistically significant at both one and two years from the time of diagnosis and treatment.  However, the fluorescence-guided surgery did not significantly decrease the rate of progression from the non-muscle invasive bladder cancer to muscle-invasive bladder cancer, as reported in the 13 September 2013 issue of PLoS One.

Urologists at University Medical Centre Hamburg-Eppendorf in Hamburg, Germany, recently conducted a similar systematic review, again drawing from various databases.  Compared to the standard approach, PDD increased the detection of papillary tumors by up to 29%, and flat carcinoma in situ (CIS) by 25-30%.  PDD also reduced the rate of residual tumors after surgery by an average of 20%, and recurrence rates were also significantly reduced. Once again, however, PDD did not appear to reduce the overall progression of the disease, as reported in the October 2013 issue of European Urology.

As you can see, these two independent analyses have arrived at the same basic conclusion:  PDD/blue-light cystoscopy can significantly improve the detection of bladder tumors while also improving surgical outcomes when compared with standard surgery in white light.  Though more randomized clinical trials are needed, the research to date has shown that PDD may be especially helpful for detecting the less conspicuous bladder lesions (smaller, flatter tumors), with the consequence of lowering the recurrence rate and decreasing the need for repeat cystoscopy.

To further improve disease control and sustain longer-term remissions, it may be ideal to consider using photodynamic therapy (PDT) to directly treat more bladder tumors that are picked up by the PDD/blue light approach, rather than relying on  standard surgery at that point.  More clinical trials are needed to assess the value of this “to see and to treat” photodynamic strategy.

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Sources

Yuan H, Qiu J, Liu L, Zheng S, Yang L, Liu Z, Pu C, Li J, Wei Q, Han P. Therapeutic outcome of fluorescence cystoscopy guided transurethral resection in patients with non-muscle invasive bladder cancer: a meta-analysis of randomized controlled trials. PLoS One. 2013 Sep 13;8(9):e74142.

Rink M, Babjuk M, Catto JW, Jichlinski P, Shariat SF, Stenzl A, Stepp H, Zaak D, Witjes JA. Hexyl aminolevulinate-guided fluorescence cystoscopy in the diagnosis and follow-up of patients with non-muscle-invasive bladder cancer: a critical review of the current literature. Eur Urol. 2013 Oct;64(4):624-38.

Yang LP. Hexaminolevulinate Blue Light Cystoscopy: A Review of Its Use in the Diagnosis of Bladder Cancer. Mol Diagn Ther. 2013 Nov 19. [Epub ahead of print]

Karaoglu I, van der Heijden AG, Witjes JA. The role of urine markers, white light cystoscopy and fluorescence cystoscopy in recurrence, progression and follow-up of non-muscle invasive bladder cancer. World J Urol. 2013 Oct 29. [Epub ahead of print]

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